Allograft Rejection of Small Bowel Transplantation in Pigs

Abstract

Small bowel allograft rejection in large animals has yet to be well defined. There are no specific early signs of graft rejection. The present experiments were undertaken to compare acute small bowel allograft rejection in pigs with and without FK506 and also to examine the usefulness of mucosal biopsies. Thirty-six outbred Large-White pigs were divided into (1) group 1 (n = 9): nonimmunosuppressed recipients; (2) group 2 (n = 8): FK506-immunosuppressed recipients; (3) group 3 (n = 2): autotransplant controls; and (4) donors (n = 17). Orthotopic small bowel transplantations were performed with Thiry-Vella loops for daily biopsies. The survival rate of group 2 was significantly longer than that of group 1 (P < 0.05). One best survivor in group 2 was killed at postoperative day (POD) 365. Treatment by FK506 prevented rejection, but most of the pigs died of pneumonia. In group 1, rejection began on POD 3 and progressed to severe rejection rapidly within 7 days. In group 2, rejection began from POD 6 to POD 8, but either remained mild or spontaneously improved. The differences in the routine laboratory data and the tumor necrosis factor-alpha level were not evident between the groups. Histological studies of repeated graft biopsies are thus considered to be essential for detecting signs of graft rejection.

Review of Various Techniques of Small Bowel Transplantation in Pigs

“…The applied dosage of heparin is 100 [17] -300 [13] IU/Kg or 2000 [5,12] -5000 IU [15]. Besides systemic heparinization, heparin is also occasionally added to the flushing solution [4,18,19]. Other forms of application [20,21] or no heparinization at all [11,17,22,23] have been reported as well.…”

“…Other forms of application [20,21] or no heparinization at all [11,17,22,23] have been reported as well. Both systemic [5, 10-12, 16, 21, 22, 24] perfusion and flushing of the bowel during back-table procedures [4,14,15,25] have been described. Systemic perfusion of the graft is mainly performed by cannulating the infrarenal aorta [5, 10-12, 16, 21, 22, 24].…”

“…In case of ex situ flushing, it is performed through the SMA [4,14,15,[24][25][26][27]. In most models, iced Lactated Ringers Solution [4,12,17,24,25,27] or University of Wisconsin Solution is used as perfusion solution [7,11,13]. Occasionally, HTK (Histidine-Triptophane-Ketoglutarate) solution [5], Institut-George-Lopez-Solution [17] or Euro Collins Solution [20,22] have also been used.…”

“…The main complications in patients include graft rejection and infections [2,3]. For research purposes in the field of SBTx the porcine model is optimal because of anatomical and physiological similarities to humans [3,4,5]. Originally, the first described SBTx was performed in a dog model by Lillehei et al in 1959 [6], and it was followed in 1970 by the first description of a complete small bowel transplantation in a pig model performed by Keaveny et al [7].…”

Models of Short Bowel Syndrome in Pigs: A Technical Review

“…In the last decade, modern therapeutic options such as tissue engineering [9] have been among the topics of interest. Due to the anatomical and physiological similarities to humans, porcine models are useful for optimizing different therapeutic approaches [10,11,12,13,14]. There are various and sometimes not exact definitions of SBS in the literature.…”